Freeze drying of human serum albumin (HSA) nanoparticles with different excipients

Abstract

Freeze drying is a suitable technique to improve the long-term storage stability of colloidal drug carrier systems such as nanoparticles. Aim of this study was to systematically evaluate excipients for the freeze drying and long-term stability of albumin-based nanoparticles. In our study, nanoparticles made of human serum albumin (HSA) were freeze dried in the presence of different cryoprotective agents and after reconstitution were evaluated with regard to their physico-chemical characteristics. Empty, doxorubicin-loaded, and PEGylated nanoparticles were prepared and were freeze dried in the presence of different concentrations of sucrose, trehalose, and mannitol, respectively. The samples were physico-chemically characterised with regard to lyophilisate appearance, particle size, and polydispersity using photon correlation spectroscopy. For evaluation of long-term stability, the samples were stored at 2-8, 25, and 40 degrees C over predetermined time intervals. In the absence of cryoprotectants, particle growth was observed in all freeze-dried formulations. In the presence of sucrose, mannitol, and trehalose aggregation of HSA nanoparticles during the freeze-drying procedure was prevented. Although all of the excipients were identified to be suitable stabilisers for freeze drying of HSA nanoparticles, sucrose and trehalose were superior to mannitol, especially with regard to the long-term storage stability results.